EAG1 enhances hepatocellular carcinoma proliferation by modulating SKP2 and metastasis through pseudopod formation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-10-24

AUTHORS

Jun Chen, Zefeng Xuan, Wenfeng Song, Weili Han, Hao Chen, Yehui Du, Haiyang Xie, Yongchao Zhao, Shusen Zheng, Penghong Song

ABSTRACT

Ether-à-go-go-1 (EAG1), one of the potassium channels, is involved in various physiological processes and plays an important role in the tumorigenesis of many kinds of cancer. EAG1 is highly expressed in hepatocarcinoma cells and is closely related to clinical prognosis, but the molecular mechanism remains elusive. In this study, we verified that EAG1 promotes the proliferation of hepatocellular carcinoma (HCC) both in vitro and in vivo. It promotes cell cycle progression by inhibiting the ubiquitination of SKP2. In addition, EAG1 promotes the migration and invasion of HCC by promoting cell pseudopod formation. Furthermore, in a high-pressure plasmid-injected mouse liver orthotopic carcinoma model, astemizole, an EAG family blocker, can significantly inhibit the formation of liver cancer. Meanwhile, liver-specific EAG1 knockout mice show resistance to hepatocarcinogenesis. This research demonstrated that EAG1 plays an important role in the progression of HCC, and could be a potential therapeutic target for HCC. More... »

PAGES

163-176

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-020-01522-6

DOI

http://dx.doi.org/10.1038/s41388-020-01522-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1132028865

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33097858


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32 schema:description Ether-à-go-go-1 (EAG1), one of the potassium channels, is involved in various physiological processes and plays an important role in the tumorigenesis of many kinds of cancer. EAG1 is highly expressed in hepatocarcinoma cells and is closely related to clinical prognosis, but the molecular mechanism remains elusive. In this study, we verified that EAG1 promotes the proliferation of hepatocellular carcinoma (HCC) both in vitro and in vivo. It promotes cell cycle progression by inhibiting the ubiquitination of SKP2. In addition, EAG1 promotes the migration and invasion of HCC by promoting cell pseudopod formation. Furthermore, in a high-pressure plasmid-injected mouse liver orthotopic carcinoma model, astemizole, an EAG family blocker, can significantly inhibit the formation of liver cancer. Meanwhile, liver-specific EAG1 knockout mice show resistance to hepatocarcinogenesis. This research demonstrated that EAG1 plays an important role in the progression of HCC, and could be a potential therapeutic target for HCC.
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41 astemizole
42 blockers
43 cancer
44 carcinoma
45 carcinoma model
46 carcinoma proliferation
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48 cells
49 channels
50 clinical prognosis
51 cycle progression
52 ether
53 formation
54 hepatocarcinogenesis
55 hepatocarcinoma cells
56 hepatocellular carcinoma
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59 invasion
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61 kind
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63 knockout mice
64 liver cancer
65 mechanism
66 metastasis
67 mice
68 migration
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70 molecular mechanisms
71 physiological processes
72 potassium channels
73 potential therapeutic target
74 process
75 prognosis
76 progression
77 progression of HCC
78 proliferation
79 pseudopod formation
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86 tumorigenesis
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